Systemic mastocytosis (SM) can be classified into indolent SM (little or no evidence of impaired organ function), aggressive SM (presence of impaired organ function), SM associated hematologic non-mast cell disease (SM-AHNMD) and mast cell leukemia. Clinical presentation in adult SM is heterogenous and includes skin disease (usually urticaria pigmentosa), mast cell mediator-release symptoms (headache, flushing, lightheadedness, syncope, anaphylaxis, etc), and direct or indirect organ damage (bone pain from lytic bone lesions, osteoporosis or bone fractures, hepatosplenomegaly, cytopenia from bone marrow involvement). In addition, around 20% of patients with SM may display significant and sometimes isolated blood eosinophilia (Tefferi and Pardanani 2004).
In general, mast cell leukemia is a terminal disease with survival measured in months and no effective therapy to date. The natural history of indolent SM is far better with median survival measured in decades and infrequent progression to aggressive SM and SM-AHNMD. Outcome in SM-AHNMD is determined by the associated AHNMD and is significantly worse than SM without AHNMD. In both indolent and aggressive SM without AHNMD, increased bone marrow mast cell and eosinophil content, elevated serum alkaline phosphatase, anemia, and hepatosplenomegaly have been associated with poor prognosis (Tefferi and Pardanani 2004). Complete histologic and clinical remission has been achieved in patients with SM associated with the FIP1L1-PDGFRα gene fusion when treated with Gleevec® (Pardanani 2003a, Pardanani 2003b).